Apparatus and methods for delivering hemostatic materials for blood vessel closure

ABSTRACT

Apparatus for sealing a vascular wall penetration disposed at the end of the tissue tract comprises a shaft, an occlusion element, a hemostatic implant, and a protective sleeve. The apparatus is deployed through the tissue tract with the occlusion element temporarily occluding the vascular wall penetration and inhibiting backbleeding therethrough. The hemostatic implant, which will typically be a biodegradable polymer such as collagen carrying an anti-proliferative agent or coagulation promoter, will then be deployed from the sealing apparatus and left in place to enhance closure of the vascular wall penetration with minimum scarring. The implant may be radiopaque to allow observation before release.

CROSS-REFERENCES TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.13/452,656 (Attorney Docket No. 28863-718.502), filed Apr. 20, 2012, nowU.S. Pat. No. ______, which is a continuation-in-part of applicationSer. No. 12/492,779 (Attorney Docket No. 28863-718.201), filed on Jun.26, 2009, which claims the benefit of provisional Application No.61/077,104 (Attorney Docket No. 28863-718.101), filed on Jun. 30, 2008;and is also a continuation-in-part of application Ser. No. 11/772,718(Attorney Docket No. 28863-715.501), filed on Jul. 2, 2007, which was acontinuation-in-part of application Ser. No. 11/302,951 (Attorney DocketNo. 28863-715.201), filed on Dec. 13, 2005, now U.S. Pat. No. 7,691,127,the full disclosures of which are incorporated herein by reference.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates generally to medical devices and methods.More particularly, the present invention relates to apparatus andprotocols for closing arteriotomies and other vascular wallpenetrations.

Angiography, angioplasty, atherectomy, and a number of other vascularand cardiovascular procedures are performed intravascularly and requirepercutaneous access into the patient's vasculature, most often into thearterial vasculature. The most common technique for achievingpercutaneous access is called the Seldinger technique, where access toan artery, typically the femoral artery in the groin, is firstestablished using a needle to form a “tract,” i.e., a passage throughthe tissue overlying the blood vessel. The needle tract is then dilated,and an access sheath is placed into the dilated tract and through apenetration in the vascular wall, such as an arteriotomy to allow theintroduction of guidewires, interventional catheters, catheter exchange,and the like to perform the desired procedure.

Once the desired procedure is completed, the access sheath must beremoved and the arteriotomy or other vascular wall penetration closed.For many years, such closure was achieved by applying manual pressureonto the patient's skin over the site of the vascular wall penetration.Patients, however, have often been heparinized to limit the risk ofthrombosis during the procedure, and clotting of the vascular wallpenetration can often take an extended period, particularly when thepenetration is relatively large for performing procedures needing largerdiameter catheters. For these reasons, improved methods for closing andsealing vascular wall penetrations have been sought.

In the last decade, a variety of new procedures and devices have beenintroduced to more effectively seal the arteriotomies and other vascularwall penetrations associated with percutaneous intravascular access.Some of the new protocols rely on suturing, others rely on clipping,plug placement, energy-based closure, and the like. One problem withmany of the new procedures, however, is that they leave material behind,and/or induce scar formation at the access site. Both the leaving ofmaterials and the formation of scar tissue can be problematic,particularly if the patient requires subsequent access to the samevascular site for performance of another vascular or cardiovascularprocedure.

For these reasons, it would be advantageous to provide protocols andapparatus which would leave no material behind and which would furtherlimit the likelihood of forming scar tissue after the procedure iscomplete. One device that can meet these objectives in many instances isthe Boomerang Catalyst™ system available from Cardiva Medical, Inc.,assignee of the present application. The Boomerang Catalyst systemincludes an expansible element at its tip for providing temporaryhemostasis when placed in the blood vessel adjacent to the vascular wallpenetration. The catheter further includes a catalytic material on itsshaft which helps induce hemostasis and clotting within the tissue tractimmediately above the vessel wall penetration. The construction and useof this system is described in copending application Ser. No. 11/302,951(Attorney Docket No. 021872-002200US); Ser. No. 11/772,718 (AttorneyDocket No. 021872-002210US); and Ser. No. 11/614,276 (Attorney DocketNo. 021872-002400US), the full disclosures of which are incorporatedherein by reference.

Despite the success of the Boomerang Catalyst systems, there may stillbe some instances where hemostasis is not achieved as rapidly. For thisreason, it would be desirable to provide further improved systems andprotocols for closing and sealing arteriotomies and other vascular wallpenetrations, where the closure may be achieved with rapid hemostasis,with a minimum risk of scar formation, and without leaving any materialsor implants permanently behind in the vessel or the tissue tract. Atleast some of these objectives will be met by the inventions describedbelow.

2. Background of the Invention

U.S. Pat. No. 7,335,219 describes a device for delivering a plug ofhemostatic material to a location just above a blood vessel wallpenetration. The hemostatic material is encapsulated in a dissolvablestructure and a non-expandable control tip assembly helps advance thedevice through the tissue tract and may also provide hemostasis andbleedback. US2007/0123817 and U.S. Pat. No. 7,008,439 describe apparatusfor sealing a vascular wall penetration. Other apparatus for closingblood vessel wall punctures are described in U.S. Pat. Nos. 4,744,364;5,061,271; 5,728,133; and 7,361,183 and U.S. Published PatentApplication Nos. 2003/0125766; 2004/0267308; 2006/0088570; 2007/0196421;and 2007/0299043. The incorporation of anti-proliferative materials inhemostatic materials for blood vessel closure and other purposes isdescribed in U.S. Pat. Nos. 7,025,776 and 7,232,454; 6,554,851; and U.S.Published Patent Application Nos. 2005/0004158; 2005/0038472;2007/0060895/2007/0032804; and 2008/0039362.

BRIEF SUMMARY OF THE INVENTION

The present invention provides apparatus and methods for sealing a bloodvessel wall penetration with little or no material being permanentlyleft behind and with a reduced likelihood of scar tissue formation. Theinvention relies on placing a hemostatic implant in the tissue tract ata location over the vascular wall penetration while the penetration istemporarily closed with an expansible occlusion element present in theblood vessel lumen. The hemostatic implant is preferably biodegradable,typically over a period of less than one year, preferably over a periodof less than six months, more preferably less than three months, and maycarry an anti-proliferative agent to reduce scar formation. Additionallyor alternatively, the implant may carry a coagulation promoter toaccelerate hemostasis and/or radiopaque material to enhancevisualization. The use of the hemostatic implant together with thetemporary hemostasis provided by the occlusion element increases thelikelihood that even relatively large vascular penetrations can besuccessfully closed and usually reduces the time needed to achieve suchclosure.

Apparatus according to the present invention for sealing a blood vesselwall penetration disposed at an end of a tissue tract comprise a shaft,an occlusion element, a hemostatic implant, and a protective sleeve. Theshaft has a proximal and distal end and is adapted to be introducedthrough the tissue tract so that the shaft distal end can be positionedwithin the blood vessel lumen. Usually, the shaft will be adapted sothat it can be introduced through the vascular access sheath which is inplace after performance of the interventional procedure.

The occlusion element is disposed near the distal end of the shaft andis configured so that it may be shifted between a radially contractedconfiguration which facilitates introduction through the tissue tractand a radially expanded configuration for deployment within the bloodvessel to occlude the penetration and provide temporary hemostasis. Thehemostatic element could be a balloon or other inflatable structure, butwill more usually be an expansible braid, coil, or other element whichmay be radially expanded by axial foreshortening. Typically, the shaftcomprises an outer tube and an inner rod where a distal end of theocclusion element is attached to a distal end of the rod and a proximalend of the occlusion element is attached to a distal end of the outertube. Thus, the occlusion element can be expanded and contracted byretracting and advancing the rod relative to the tube, respectively. Thepreferred occlusion element comprises a braided mesh covered with anelastic membrane. As described thus far, the shaft and occlusion elementmay be similar or identical to those described in the earlier referencedcommonly owned patent applications.

The hemostatic implant of the present invention is disposed over anexterior surface of the shaft proximal to the occlusion element. Theprotective sleeve is retractably disposed over the hemostatic implant toprotect it while the shaft is being introduced to the tissue tract. Thehemostatic implant will typically comprise a body or wrapped sheet whichpartially or fully circumscribes the shaft, but other configurationscould also be utilized. In a first embodiment, the hemostatic implantcomprises a cylindrical body which is coaxially mounted about the shaftof the delivery device. Such fully circumscribing implants, however, canhave difficulty being released from the shaft after they are exposed andhydrated. Thus, it will often be preferable to provide hemostaticimplant configurations where the body partially circumscribes the shaftor is disposed in parallel to the shaft. When the implant is notdisposed about the shaft, release upon rehydration will be greatlysimplified as the rehydrated implant will lie adjacent to the shaft,allowing the shaft and the collapsed occlusion element to be drawnproximally past the rehydrated hemostatic implant with minimuminterference. The hemostatic implant typically comprises a swellable,biodegradable polymer which swells upon hydration. Hydration isprevented when the polymer is introduced by the protective sleeve. Thepolymer hydrates and swells when the sleeve is retracted within thetissue tract, exposing the polymer to the body fluids. Suitable polymersinclude biodegradable hydrogels such as polyethylene glycols, collagens,gelatins, and the like.

An anti-proliferative agent will usually be distributed within orotherwise carried by the material of the hemostatic implant. As mostanti-proliferative agents, such as sirolimus, paclitaxel, and the like,are hydrophobic, it will usually be desirable to incorporate theanti-proliferative agents in a carrier, such as a biodegradable polymer,such a polylactic acid (PLA), poly(lactide-co-glycolide), and the like.The anti-proliferative agents may be incorporated into pores ofpolymeric beads or other structures which are dispersed or distributedwithin the biodegradable hydrogel or other swellable polymer. In certainembodiments, the anti-proliferative agents may be incorporated intonanoparticles, typically having dimensions in the range from 10 nm to100 .mu.m.

Agents useful as coagulation promoters, such as thrombin, tissuefactors, components of the clotting cascade, and the like may also beincorporated into the body of the hemostatic implant. In some instances,it may be desirable to incorporate such coagulation promoters intoparticulate or other carriers as described above with regard to theanti-proliferative agents.

In addition to the anti-proliferative agents and the coagulationpromoters, the hemostatic implants of the present invention may furtherincorporate radiopaque materials in or on at least a portion of theimplant body. For example, a radiopaque material, such as barium, may beincorporated into the polymer, either by dispersion or chemical bonding.Alternatively, radiopaque rings, markers, and other elements, may beattached on or to the hemostatic implant, for example at each end of theimplant to facilitate visualization of the implant as it is beingimplanted. Additionally or alternatively, radiopaque markers may beprovided on the tube or shaft which carries the hemostatic implant sothat the marker(s) align with a portion of the implant, typically eitheror both ends of the implant, prior to deployment.

In a preferred aspect of the present invention, the protective sleeve isheld in place by a latch mechanism while it is being introduced. Aseparate key element is provided to release the latch mechanism andpermit retraction of the sleeve after the device has been properlyplaced through the tissue tract and into the target blood vessel. Thelatch will be disposed on the shaft and will engage the protectivesleeve to immobilize the sleeve during introduction. The key, which isusually slidably disposed on the shaft proximal of the latch, is able toshift the latch between a locking configuration where the sleeve isimmobilized and an open configuration which allows the sleeve to beproximally retracted. Usually, the latch is spring-loaded to deflectradially outwardly from the shaft in a manner which engages the sleeve.The key is then adapted to radially depress the latch to release thesleeve. In a preferred embodiment, the latch and key mechanism willextend over a proximal portion of the shaft having a length sufficientto allow manual access to the key latch even when the shaft is placed inthe tissue tract.

In a further preferred aspect of the present invention, a backstopstructure is provided on the shaft to engage the hemostatic implant toimmobilize the implant while the sleeve is being proximally refracted.The backstop usually comprises a tube disposed on or coaxially over theshaft and having a distal end which engages a proximal end of thehemostatic implant. The backstop engages the hemostatic implant toprevent accidental dislodgement while the occlusion element is beingproximally retracted through the implant. The backstop may include aspace or receptacle for receiving the retracted occlusion element,allowing the backstop to be held in place until the occlusion elementhas been fully retracted through the hemostatic implant.

The protective sleeve of the present invention may comprise an outersleeve and a separately retractable inner release sheath. The outersleeve and inner release sheath are usually mounted coaxially so thatthe outer sleeve may be retracted over the inner release sheath whilethe inner release sheath remains stationary over the implant and acts asa friction barrier between the outer sleeve and implant. Without theinner release sheath, the protective sleeve, which applies thecompressive and constrictive forces to the hemostatic implant, couldstick to the hemostatic implant and make retraction of the protectivesleeve and deployment of the implant difficult. The inner release sheathis preferably axially split so that, once the outer sleeve is retracted,the inner release sheath opens to release the implant and facilitateretraction of the release sheath. In preferred embodiments, the outersleeve can engage the inner release sheath after the outer sleeve hasbeen partly retracted. During the remainder of the outer sleeveretraction, the outer sleeve will then couple to and retract the innerrelease sheath to fully release the hemostatic implant. In addition tothe use of the inner release sheath, the distal end of the protectivesleeve may be sealed with a biodegradable substance, such as a glyceringel, which can inhibit premature hydration of the hemostatic implantprior to release.

In a further preferred aspect of the present invention, the key of thelatch mechanism can include a coupling element which attaches to theprotective sleeve as the key is advanced and the latch is released.After the key couples to the protective sleeve, the key can be used toretract the protective sleeve. That is, rather than having to repositionthe hand to grab and retract the protective sleeve which would alsoretract the mating key, only the key needs to be held and retracted.

Methods according to the present invention for sealing a blood vesselpenetration disposed at the end of a tissue tract comprise providing anapparatus including a shaft, an occlusion element, and a hemostaticimplant disposed on an exterior surface of the shaft. The shaft isintroduced through the tissue tract to position the occlusion element inthe lumen of the blood vessel and the hemostatic implant within thetissue tract. The hemostatic implant is covered by a protective sleevewhile the shaft is being introduced through the tissue tract, and theocclusion element is deployed to temporarily inhibit blood flow from theblood vessel into the tissue tract. The protective sleeve is thenretracted to expose the hemostatic implant, where the implant typicallyabsorbs fluid and expands to provide the desired seal within the tissuetract. After the hemostatic implant has expanded sufficiently, theocclusion element will be collapsed, and the shaft and collapsedocclusion element withdrawn leaving the hemostatic implant in the tissuetract. As described above, it will usually be preferred to position thehemostatic implant laterally or to the side of the shaft which carriesthe occlusion element. By thus positioning the occlusion element tobypass the hydrated hemostatic implant, withdrawal of the collapsedocclusion element past the hydrated hemostatic implant can be greatlyfacilitated. Preferably, the material of the hemostatic implant willdegrade over time, preferably over a period of less than one year, morepreferably over a period of less than six months, usually less thanthree months, leaving no material behind at the vascular access point.

In a preferred aspect of the methods of the present invention, theprotective sleeve is latched to the shaft while the shaft is introduced.By “latched” is meant that the sleeve will be fixed or immobilized tothe shaft by some mechanical link, where the link may be selectivelydisconnected or “unlatched” when it is desired to retract the sleeve andexpose the hemostatic implant. Thus, the methods of the presentinvention will preferably further comprise unlatching the sleeve beforeretracting the sleeve. In a specific embodiment, the unlatchingcomprises distally advancing a key over the latch to effect the desiredunlatching. As described above in connection with the apparatus of thepresent invention, an exemplary latch and key comprises a spring-likeelement which is secured over an exterior portion of the shaft. Thespring-like element typically projects radially outward from the shaftwhen unconstrained. In this way, the spring-like latch element canengage the protective sleeve to prevent proximal retraction of thesleeve. The latch can be released by advancing a cylindrical or otherkey element distally over the shaft to depress the spring-like latchelement.

In a further preferred aspect of the method of the present invention, aproximal portion of the sleeve will be configured to lie proximal to,i.e., outside of, the tissue tract when the occlusion element isdeployed in the blood vessel lumen. Usually, the key element will liefurther proximal of the sleeve, permitting the user to manually deploythe key to unlock the latch and to further manually retract theprotective sleeve by manually clasping an exposed portion of the sleeveand pulling it proximally from the tissue tract. Typically, the sleevewill have a length in the range from 2 cm to 30 cm, more typically from5 cm to 15 cm.

In a still further preferred aspect of the method, the hemostaticimplant will be constrained to prevent it from being displacedproximally while the shaft is being introduced through the tissue tract.In particular, the backstop or other element may be fixed to the shaftin a location selected to engage the hemostatic implant or an extensionthereof to prevent the implant from being displaced proximally, eitheras the shaft is being introduced or more likely as the protective sleeveis being proximally retracted over the implant. Usually, the backstop orother element will be slidably mounted over the shaft so that it may beheld in place as the occlusion element is retracted past the hemostaticimplant.

In a specific aspect of the method of the present invention, radiopaquemarkers on or within the shaft or hemostatic implant are used to verifythe location of implant prior to release. Inclusion of radiopaquemarkers on the delivery shaft is particularly useful when no radiopaquematerial is incorporated within the hemostatic implant. Preferably,there will be at least two distinct radiopaque bands, with one at eachend of the implant. By observing the orientation of the two markers, thephysician can determine whether the implant is properly aligned adjacentto the vascular penetration or has inadvertently advanced into a lumenof the blood vessel prior to deployment. In particular, by measuring orvisually assessing the apparent distance between the bands when thedevice is being fluoroscopically imaged from an anterior aspect, theapparent distance between the bands will be longer if the hemostaticimplant is within the blood vessel lumen than if it is within the tissuetract immediately above the blood vessel wall penetration. Such apparentdifferences in the positions of the two radiopaque marker bands resultsfrom the foreshortening of the vertical angle at the entry through thewall penetration into the blood vessel lumen. For example, if the tissuetract is disposed at a 45.degree. angle with respect to the horizontalorientation of the blood vessel lumen, in an anterior view, the markerbands will appear to be approximately 30% closer to each other than theywould in the horizontal view when they are present in the blood vessellumen.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates an exemplary sealing apparatus constructed inaccordance with the principles of the present invention, shown insection.

FIG. 1A is a detailed view of a distal portion of the sealing apparatusof FIG. 1, shown in partial section.

FIG. 2 is a cross-sectional view of the sealing apparatus of FIG. 1,shown with an expanded occlusion element.

FIGS. 3-7 illustrate the further steps of deployment of the hemostaticimplant from the apparatus of FIGS. 1 and 2.

FIGS. 8A-8I illustrate placement and deployment of the hemostaticimplant using the apparatus of FIGS. 1 and 2 through a vascular sheathplaced in a blood vessel.

FIGS. 9A-9C illustrate a sealing apparatus in accordance with thepresent invention having a protective sleeve including an outer sleeveand an inner release sheath.

FIGS. 10A-10C illustrate a sealing apparatus in accordance with thepresent invention having a key latch mechanism which engages theprotective sleeve and may be used to proximally withdraw the sleeve todeploy the hemostatic implant.

FIGS. 11A and 11B illustrate a hemostatic implant which is coaxiallydisposed about the shaft of the deployment apparatus of the presentinvention.

FIGS. 12A and 12B illustrate the hemostatic implant which is laterallydisposed relative to the shaft of the deployment mechanism.

FIGS. 13A and 13B illustrate how aligned radiopaque markers may beutilized to determine that the hemostatic implant is properly locatedprior to deployment.

FIGS. 14A and 14B illustrate how such radiopaque markers would appearwhen the hemostatic implant is improperly positioned prior todeployment.

FIGS. 15A-15F illustrate an alternative hemostatic implant protocol.

DETAILED DESCRIPTION OF THE INVENTION

Referring to FIGS. 1 and 1A, an exemplary sealing apparatus 10constructed in accordance with the principles of the present inventioncomprises a shaft assembly 70 including an outer tube 71 and an innerrod 76. An expansible occlusion element 90 is mounted at a distal end(to the right in FIGS. 1 and 1A) of the shaft assembly 70 and includes aradially expansible mesh 74 covered by an elastomeric membrane 96. Ahandle assembly 78 is attached to a proximal end of the shaft assembly70 and is operatively attached to both the outer tube 71 and inner rod76 so that the inner rod can be axially advanced and retracted relativeto the outer tube. The inner rod 76 and outer tube 71 are coupledtogether at the distal tip of the sealing apparatus 10 by a plug 77 anda proximal anchor 75, respectively. The occlusion element 90 is heldbetween the plug 77 and the proximal anchor 75 so that axial retractionof the rod in the proximal direction (to the left as shown in FIGS. 1and 1A) foreshortens the occlusion element 90, causing the occlusionelement to expand radially, as shown for example in FIG. 2.

Axial advancement and retraction of the rod 76 relative to the outertube 71 is effected using the handle assembly 78. The handle assembly 78includes a cylindrical body 103 attached to the proximal end of theouter tube 71 by a bushing 104 so that the body 103 will remain fixedrelative to the outer tube as the inner rod 76 is retracted andadvanced. The inner rod is retracted and advanced by a slide assembly101 which includes a short tube 110 fixedly attached to an endcap 111and a slide cylinder 109. The inner rod 76 is secured by tube element107 which carries locking element 106 and bearing elements 108 and 109.Bearing element 109 is attached to proximal grip 101 and the assembly ofthe grip 101 and tube element 107 can slide freely within the interiorof the cylindrical body 103 so that the rod 76 may be proximallyretracted relative to the body 103 and outer tube 71, as shown in FIG.2. Once the expansible occlusion element 90 has been radially expanded,the rod 76 will remain retracted and is held in place by locking element106 which is pulled over a detent 105, again as shown in FIG. 2. Analignment bushing 108 is provided in the interior of the cylindricalbody 103 to maintain alignment of the slide assembly 101 relative to thecylindrical body.

The sealing apparatus of the present invention may optionally include atensioning mechanism 80 which includes a coil spring 86, a grippingelement 85, and a coupling element 87. The tensioning mechanism 80 maybe selectively positioned along the length of shaft assembly 70, andwill provide a tension determined by the constant of coil spring 86 tohold the expanded occlusion element 74 against the vascular penetration,as described in more detail in copending, commonly-owned applicationSer. No. 10/974,008, (Attorney Docket No. 021872-002010US), the fulldisclosure of which is incorporated herein by reference. As describedthus far, the construction and use of the sealing apparatus includingshaft assembly 70, handle assembly 78, tensioning mechanism 80, andexpansible occlusion element 90 are generally the same as illustrated incopending application Ser. No. 10/974,008. The present invention isdirected at modifications and improvements to the earlier device fordelivering a hemostatic implant into the tissue tract generally abovethe vascular wall penetration, as will be described in more detailbelow.

As best seen in FIG. 1A, hemostatic implant 121, which will typically bea biodegradable polymer as described in more detail above, is carriedcoaxially or in parallel over the outer tube 71 near the distal endthereof proximal to the expansible occlusion element 90. While thehemostatic implant 121 is shown to be positioned coaxially over outertube 71 in FIG. 1A, it will often be desirable to modify or repositionthe implant in order to facilitate release from the sealing apparatusafter the implant has been deployed. More simply, the hemostatic implantcould be axially split to allow it to partially open after it ishydrated and facilitate passage of the collapsed occlusion element 74 asthe sealing apparatus is being withdrawn. Alternatively, the hemostaticimplant may be reconfigured and carried laterally (i.e., to one side of)with respect to the shaft of the sealing apparatus, as described in moredetail hereinafter with respect to FIGS. 9A and 9C. The hemostaticimplant 121 could alternatively be carried on the inner surface of aprotective sleeve 123 which is slidably carried over the outer tube 71.The protective sleeve 123 slides over a backstop 127 which is slidablymounted over the outer tube 71 and which is prevented from movingproximally by stop member 125 which is fixed to the outer surface of theouter tube. Backstop 127 has a distal end 128 which engages a proximalend of the hemostatic implant 121. Thus, by proximally retracting theprotective sleeve 123, the hemostatic implant 121 can be exposed to thetissue tract and released from the sealing apparatus.

Accidental axial retraction of the protective sleeve 123 is prevented bya latch mechanism including a latch element 120 and a key 126 (FIGS. 1and 2). The latch element 120 is typically a spring-loaded component,for example a conical spring having a narrow diameter end attached tothe outer tube 71 and a flared or larger diameter end 129 which engagesa stop ring 124 formed on the inner surface of the protective sleeve123. So long as the flared end 129 of the latch element 120 remains inits flared or open configuration, as illustrated in FIG. 1A, accidentalproximal retraction of the sleeve is prevented. It is further noted thatthe stop ring 124 engages stop member 125 of the backstop 127 preventingaccidental distal movement of the protective sleeve 123. Thus, when thesealing apparatus 10 is introduced to a tissue tract, as described inmore detail below, movement of the protective sleeve 123 in either thedistal or proximal direction is inhibited.

To allow selective proximal retraction of the protective sleeve 123, thekey 126 (FIGS. 1 and 2) may be axially advanced to engage the latchingelement 120, as illustrated in FIG. 3. The key 126 fits inside of theprotective sleeve 123 and depresses or radially contracts the latchelement 120 so that it fits within the interior circumference of thestop ring 124, thus allowing proximal retraction of the protectivesleeve 123, as shown in FIG. 4.

Once the key 126 has engaged and constrained the latch element 120, asshown in FIG. 3, the protective sleeve 123 may be proximally withdrawnpast the hemostatic implant 121 and the backstop 127, as shown in FIG.4. Thus, the hemostatic implant 121 will be released from constraint andexposed to the environment in the tissue tract. The environment in thetissue tract will include blood and other body fluids which can hydratethe hemostatic implant 121, causing swelling as shown in FIG. 4. Theswelling will continue, as shown in FIG. 5, and the radially expandedocclusion element 90 can be collapsed using the handle assembly, asshown in FIG. 5. The collapsed occlusion element 90 can then beproximally withdrawn into distal receptacle 128 of the backstop assembly127, as shown in FIG. 6 (where an annular space may be provided toaccommodate the occlusion element). When the occlusion element has beenfully withdrawn within the backstop 127, the hemostatic implant iscompletely released, as shown in FIG. 6, and the remaining portions ofthe sealing apparatus can be pulled away from the hemostatic implant, asshown in FIG. 7.

Referring now to FIGS. 8A-8I, deployment and use of the sealingapparatus 10 of the present invention through an introducer sheath 40will be described in more detail. Introducer sheath 40 will typically bein place within a blood vessel lumen 41 passing from the skin surface 46through tissue 45 in a tissue tract. A vascular wall penetration 42 willthus be present in the vascular wall 43, all as shown in FIG. 8A. Thesealing apparatus 10 is then introduced through the access sheath 40 sothat the expansible occlusion element 90 passes out through the distalend of the sheath, as shown in FIG. 8B. Handle assembly 78 will remainoutside of the sheath and accessible to the user so that the slideassembly 101 may be pulled relative to the cylindrical body 103 toradially expand the occlusion element 90, as shown in FIG. 8C. Thevascular access sheath 40 may then be withdrawn over the exterior of thesealing apparatus 10 while the sealing apparatus is simultaneouslywithdrawn to seat the expanded occlusion element 90 against the vascularpenetration 42, as shown in FIG. 8D.

At that point, the protective sleeve 123 and key 126 become exposed andavailable to the user for manipulation. The key may then be distallyadvanced over the outer tube 71 so that the key engages and depressesthe latch 120 (FIG. 1A) as illustrated in FIG. 8E. The key 126 andprotective sleeve 123 may then be manually pulled in a proximaldirection over the outer tube 71 to release the hemostatic implant 121,as shown in FIG. 8F. The expandable element 90 may then be collapsed, asshown in FIG. 8G, and the collapsed element withdrawn into thereceptacle 128 of the backstop 127 of the sealing apparatus, as shown inFIG. 8H. The entire sealing apparatus 10, except for the hemostaticimplant 121, may then be withdrawn from the tissue tract, leaving thehemostatic implant 121 in place over the now closed vascular wallpenetration, as shown in FIG. 8I. The hemostatic implant, which mayoptionally carry the anti-proliferative, coagulation promoting, and/orradiopaque substances described above, will remain in place inhibitingbleeding and allowing the vascular wall penetration to heal. Over time,the hemostatic implant 121 will preferably biodegrade, leaving a healedtissue tract and vascular wall penetration which are usually suitablefor re-entry at a subsequent time.

Referring now to FIGS. 9A-9C, a protective sleeve 123′ comprises anouter sleeve 150 and an inner release sheath 152. The outer sleeve 150and inner release sheath 152 are separately retractable so that theouter sleeve may first be retracted relative to the hemostatic implant121 (FIG. 9B) while the inner release sheath initially remains over theimplant. The release sheath 152 will thus provide an anti-frictioninterface so that the outer sleeve 150 slides over the implant 121 withreduced sticking The inner release sheath 152 is preferably formed froma relatively lubricious or slippery material and will preferably includean axial opening or slit 158 which permits the distal portion thereof topartially open after the outer sleeve 150 has been retracted, as shownin FIG. 9B. Once the outer sleeve 150 has been retracted to relieveconstraint over the hemostatic implant, the inner sleeve may then beretracted to completely release the hemostatic implant, as shown in FIG.9C. Conveniently, the outer sleeve 150 may be coupled to the innerrelease sheath 152 so that proximal retraction of the outer sleeve willautomatically retract the inner release sheath at the proper point intravel. For example, a cavity or channel 154 may be formed in an innersurface of the outer sleeve 150 and a ring or other engaging element 156may be formed on the outer surface of the inner release sheath 152.Initially, the ring 156 will be positioned at the proximal end of thecavity or channel 154, as shown in FIG. 9A. After the outer sleeve 150has been retracted so that it no longer lies over the implant 121, thering may then engage a distal end of the cavity or channel 154, as shownin FIG. 9B, and engage the ring 156, allowing the outer sleeve to thenpull the inner sleeve proximally, as shown in FIG. 9C, to fully releasethe hemostatic implant 121.

Referring now to FIGS. 10A-10C, it is also possible to selectivelycouple the key 126′ to a protective sleeve 123′. The key 126′ has acoupling element, such as plurality of proximally disposed barbs 160 atits distal end. The key 126′ may be advanced into the protective sleeve123′ where a distal end 162 of the key 126′ engages latching element120′ on the outer tube 71′. Latching mechanism 120′ may convenientlycomprise a plurality of barbs so that advancement of the key 123′radially closes the barbs allowing the protective sleeve 123′ to beproximally retracted relative to the tube 71′. Once the key 126′ isfully distally advanced, as shown in FIG. 10B, the proximally disposedbarbs 160 will engage an inner lip 164 at the proximal end of theprotective sleeve 123′. Thus, as the key 126′ is proximally retracted,as shown in FIG. 10C, the key will pull the protective sleeve 123′ in aproximal direction, thus exposing the implant 121.

A further aspect of the present invention is illustrated in FIGS. 10Aand 10B. Radiopaque marker bands 170 and 172 may be provided at theproximal and distal ends of the implant 121, respectively. Usually,these bands will be disposed on the outer tube 71′, but they could alsobe disposed on or incorporated within the hemostatic implant 121. Ineither case, they are useful to evaluate positioning of the hemostaticimplant prior to deployment, as described in more detail below in FIGS.13A, 13B, 14A, and 14B.

Referring now to FIGS. 11A and 11B, the hemostatic implant 121 may bedisposed coaxially over the outer tube 71 and in a rod 76. By proximallyretracting the protective sleeve 123, the implant 121 is released andcan hydrate as shown in FIG. 11B. As described previously, however, itwill still be necessary to withdraw the outer tube 71 as well as thecollapsed occlusion element 90 past the hemostatic implant 121. When thehemostatic implant 121 fully circumscribes the outer tube 71, however,both the tube 71 and the collapsed occlusion element 90 can tend todislodge the implant within the tissue tract.

Therefore, in some instances, it will be desirable to modify thegeometry of the implant to facilitate withdrawal of the outer tube andthe collapsed occlusion element. For example, as shown in FIGS. 12A and12B, hemostatic implant 121′ can be formed with a crescent-shapedcross-section so that it does not fully circumscribe the outer tube 71which carries it. By laterally displacing the outer tube 71 and innerrod 76 within the protective sleeve 123, as shown in FIG. 12A, thevolume of the hemostatic implant 121 will be generally the same as thatshown in FIG. 11A. When the protective sleeve 123 is withdrawn, however,as shown in FIG. 12B, the hemostatic implant 121 will hydrate and expandlaterally on one side of the outer tube 71, as shown in FIG. 12B. Bydisposing the outer tube 71 and collapsed occlusive element 90 to oneside of the implant, it is much easier to withdraw the apparatus andcollapsed occlusion member past the implant without dislodging theimplant within the tissue track.

Referring now to FIGS. 13A and 13B, the radiopaque markers 170 and 172can be used to determine whether the hemostatic implant 121 is orientedproperly prior to deployment. For simplicity, the protective sleeve andother components of the deployment system are not shown in FIGS. 13A and13B (or in 14A and 14B as described below). The radiopaque markers 170and 172 may be formed as part of the deployment instrument, for examplebeing placed on outer tube 71, and/or may be formed as part of thehemostatic implant 121. In either case, when the deployment apparatus isproperly oriented as shown in FIG. 13A, the radiopaque markers 170 and172 will appear to be stacked generally vertically when viewed in ananterior view, as shown in FIG. 13B. In contrast, if the apparatus hasbeen improperly deployed so that the hemostatic implant has beenadvanced into the vessel lumen past the tissue tract TT as shown in FIG.14A, then the radiopaque markers 170 and 172 will be spaced apart in theanterior view as shown in FIG. 14B. As these views will be readilydistinguishable by the physician using conventional fluoroscopy, theradiopaque markers provide a convenient and reliable indicator of whenit is acceptable to deploy the hemostatic implant.

Referring now to FIGS. 15A through 15F, a method for hemostasis of apuncture site in a body lumen employing the device 270 of FIG. 1 isillustrated. FIG. 15A depicts an existing introducer sheath 240 advancedthrough an opening in a skin surface 246, tissue tract in fascia 245 andvessel wall 243 and seated in a vessel lumen 241 at the completion of acatheterization procedure. Device 270 is then inserted through the hubof the sheath 240 and is advanced until the expansible member 274 isoutside the sheath 240 and in the vessel lumen 241, as shown in FIG.15B. This positioning may be indicated by a mark or feature on thecatheter 271 or the handle assembly 278.

As shown in FIG. 15C, the expansible member 274 is then deployed byoperation of the handle assembly 278. The sheath 240 is then slowlypulled out of the body, placing the expansible member 274 against theinner wall of the vessel 243 at the puncture site 242. As the sheath 240is removed, the grip member 285 which is slidably disposed over thecatheter shaft 2 71 and the handle assembly 278 are revealed. Sheath 240is then discarded, leaving deployed expansible member 274 seated at thepuncture site 242 and the bio-chemical chamber/region 351 in the tissuetract 247 as shown in FIG. 15D. If the device is equipped with thesafety seal 355 as in device 270, then the safety seal 355 is removed bypulling the tab 356 proximally along the catheter shaft.

Referring now to FIG. 15E, once safety seal 355 is removed, the gripelement 285 is grabbed and pulled in a proximal direction. Grip 285 ismoved proximally to provide adequate amount of tension to the deployedexpansible member 274 to achieve hemostasis. Typically, the amount oftension applied to the expansible member 274 is in the range of 0.5ounces to 30 ounces. In particular, proximal movement of grip 285 causessimultaneous elongation of the tensioning coil 286, causing theexpansible member to locate and temporarily close the puncture site 242,and displacement of the bio-chemical seal 353, exposing the bio-chemicalagent 352 to the surrounding tissue at a predetermined distance from thepuncture site. The elongated position of coil 86 is maintained byapplication of a small external clip 250 to the catheter and seatedagainst the surface of the skin 246, as shown in FIG. 15E. Device 270 isleft in this position for a period of time to allow the bio-chemicalagent 352 to reconstitute with the fluids in the tissue tract 247,generating coagulum. Clip 250 is then removed and the expansible member274 is collapsed by manipulation of the handle assembly 278. Device 270is then removed, leaving the active bio-chemical agents 352 and thecoagulum in the tract 247 and adjacent the vessel puncture site 242, asshown in FIG. 15F. Additional finger pressure at the puncture site maybe required to allow the coagulum to seal the small hole left in thevessel wall after removal of the device.

While the above is a complete description of the preferred embodimentsof the invention, various alternatives, modifications, and equivalentsmay be used. Therefore, the above description should not be taken aslimiting the scope of the invention which is defined by the appendedclaims.

What is claimed is:
 1. A method for sealing a blood vessel penetrationdisposed at the end of a tissue tract, said method comprising: providingan apparatus including a shaft, an occlusion element at a distal end ofthe shaft, a hemostatic implant disposed on an exterior surface of theshaft, and an outer sleeve constraining the implant on the shaft;introducing the shaft through the tissue tract to position the occlusionelement in a lumen of the blood vessel and the hemostatic implant withinthe tissue tract, wherein the hemostatic implant is covered by the outersleeve while the shaft is being introduced; deploying the occlusionelement to inhibit blood flow from the blood vessel into the tissuetract; retracting the outer sleeve to expose the hemostatic implantwherein the hemostatic implant is axially split and configured to remainstationary on the shaft while the outer sleeve is being retracted and toopen laterally to release from the shaft after the outer sleeve is fullyretracted from over the implant; collapsing the occlusion element; andwithdrawing the shaft and collapsed occlusion element past thehemostatic implant which remains in the tissue tract.
 2. A method as inclaim 1, wherein the hemostatic implant is prevented from beingdisplaced proximally by a back stop on the shaft while the outer sleeveis retracted.
 3. A method as in claim 1, wherein the apparatus furtherincludes an inner release sheath inside of the outer sleeve and coveringthe implant, wherein the outer sleeve is retracted first while the innerrelease sheath inhibits sticking between the outer sleeve and thehemostatic implant.
 4. A method as in claim 3, wherein the inner releasesheath is split so that it opens over the hemostatic implant after theouter sleeve is retracted.
 5. A method as in claim 1, wherein thehemostatic implant comprises a cylindrical body which circumscribes theshaft having at least one axial split along its length.
 6. A method asin claim 1, wherein the hemostatic implant comprises a swellable,biodegradable polymer, wherein the polymer is not fully hydrated whencovered by the outer sleeve.
 7. A method as in claim 6, wherein thebiodegradable polymer comprises a material selected from the groupconsisting of polyethylene glycols, collagens, and gelatins.
 8. A methodas in claim 1, wherein the hemostatic implant comprises ananti-proliferative agent selected from the group consisting ofsirolimus, paclitaxel, wherein the active agents are incorporated in adegradable carrier comprising a material selected from the groupconsisting of polylactic acid, and poly(lactide-co-glycolide).
 9. Amethod as in claim 1, wherein the hemostatic implant comprises ananti-proliferative agent selected from the group consisting of sirolimusand paclitaxel, or a coagulant selected from the group consisting ofthrombin and tissue factor.
 10. A method as in claim 1, comprising anactive agent which is incorporated in a nanoparticle.
 11. A method as inclaim 10, wherein the nanoparticles have an average size in the rangefrom 10 nm to 100 μm.
 12. A method as in claim 1, wherein at least aportion of the hemostatic implant is radiopaque, wherein the methodfurther comprises observing the hemostatic implant to determine that ithas a correct orientation before the outer sleeve is retracted.
 13. Amethod as in claim 1, wherein the shaft is advanced through anintroducer sheath which was previously placed in the tissue tract.
 14. Amethod as in claim 13, further comprising removing the introducer sheathover the apparatus after the shaft has been introduced therethrough. 15.A method as in claim 14, wherein the shaft is introduced without aguidewire.
 16. A method as in claim 1, wherein the hemostatic implantcomprises a wrapped sheet which is axially split and which partially orfully circumscribes the shaft.
 17. A method as in claim 1, wherein theouter sleeve couples to and retracts the inner release sheath to exposeand release the hemostatic implant as the outer sleeve is retraced. 18.A method as in claim 1, further comprising retracting the inner releasesheath separately from the outer sleeve after the outer sleeve has beenat least partially retraced.
 19. Apparatus for sealing a blood vesselpenetration disposed at the end of a tissue tract, a shaft having aproximal end and a distal end; a radially expandable occlusion elementat a distal end of the shaft; a hemostatic implant disposed over anexterior surface at the distal end of the shaft; and a retractable outersleeve constraining the implant on the shaft; wherein the hemostaticimplant is axially split and configured to remain stationary on theshaft while the outer sleeve is being retracted and to open laterally torelease from the shaft after the outer sleeve is fully retracted fromover the implant.
 20. An apparatus as in claim 19, further comprising aback stop on the shaft wherein the backstop is configured to prevent thehemostatic implant from being displaced proximally by while the outersleeve is retracted.
 21. An apparatus as in claim 19, wherein theapparatus further includes an inner release sheath inside of the outersleeve and covering the implant, wherein the release sheath inhibitssticking between the outer sleeve and the hemostatic implant as theouter sleeve is retracted.
 22. An apparatus as in claim 19, wherein theinner release sheath is split so that it opens over the hemostaticimplant after the outer sleeve is retracted.
 23. An apparatus as inclaim 19, wherein the hemostatic implant comprises a cylindrical bodywhich circumscribes the shaft having at least one axial split along itslength.
 24. An apparatus as in claim 19, wherein the hemostatic implanthas a crescent-shaped cross-section.
 25. An apparatus as in claim 19,wherein the hemostatic implant comprises a wrapped sheet which isaxially split and which partially or fully circumscribes the shaft. 26.An apparatus as in claim 19, wherein the outer sleeve is configured tocouple to and retract the inner release sheath to expose and release thehemostatic implant as the outer sleeve is retraced.
 27. An apparatus asin claim 19, wherein the inner release sheath is configured to beretracted separately from the outer sleeve.